Usefulness of Dobutamine Tc-99m
Sestamibi-Gated Single-Photon Emission
Computed Tomography for Prediction of
Left Ventricular Ejection Fraction
Outcome After Coronary
Revascularization for
Ischemic Cardiomyopathy
Mario Leoncini,
MD, Roberto Sciagra`,
MD, Mauro Maioli,
MD, Francesco Bellandi,
MD,
Gabriella Marcucci,
MD, Stelvio Sestini,
MD, Silvia Chiocchini,
MD, and
Roberto P. Dabizzi,
MDGated single-photon emission computed tomography (SPECT) imaging allows analysis of myocardial perfusion and assessment of baseline global and regional left ventricular (LV) function and their changes during low-dose dobutamine infusion. The study examined whether the changes in LV ejection fraction induced by dobut-amine and evaluated using technetium-99m sestamibi-gated SPECT predict the evolution of ejection fraction after revascularization in patients with ischemic cardio-myopathy. Thirty-seven patients underwent resting and dobutamine nitrate-enhanced sestamibi-gated SPECT before revascularization and baseline-resting sestamibi gated SPECT after intervention to assess global func-tional changes. A postrevascularization improvement in ejection fraction >5 U was defined as significant. At follow-up, ejection fraction increased significantly in 19
patients. According to receiver-operating characteristic curve analysis, an increase in ejection fraction >5 U during dobutamine was the optimal cutoff value for predicting a significant postrevascularization improvement, with 79% sensitivity, 78% specificity, and 78% accuracy. A signifi-cant correlation was found between dobutamine and pos-trevascularization ejection fraction (rⴝ 0.85; p <0.0001).
The increase in ejection fraction during dobutamine is a good predictor of an improvement in ejection fraction after revascularization. This represents another important diag-nostic contribution obtained using gated SPECT imaging for the assessment of myocardial viability in patients with ischemic cardiomyopathy. 䊚2002 by Excerpta
Medica, Inc.
(Am J Cardiol 2002;89:817– 821)
T
he acquisition of perfusion images using gated single-photon emission computed tomography (SPECT) allows the assessment of regional and global left ventricular (LV) function.1These additional data are useful in detecting myocardial viability.2– 4More-over, the acquisition of gated SPECT images during low-dose dobutamine infusion permits assessment of the regional contractile reserve of asynergic seg-ments.5– 8On the other hand, using gated SPECT, LV
volumes and ejection fraction can be estimated in a reliable and reproducible way.1 Thus, this study
ex-amines whether the changes in LV ejection fraction during dobutamine stimulation, evaluated using tech-netium-99m sestamibi-gated SPECT, predict changes in ejection fraction after revascularization in patients with ischemic cardiomyopathy.
METHODS
Patient group:We prospectively evaluated 63 con-secutive patients (57 men, mean age 65 ⫾ 9) with coronary artery disease and impaired LV function (mean LV ejection fraction 32 ⫾ 9%, range 9% to 49%) referred to our laboratory for viability assess-ment using dobutamine nitrate-enhanced gated sesta-mibi SPECT. Patients with recent (⬍1 month) myo-cardial infarction or unstable angina, heart disease other than coronary artery disease, atrial fibrillation, or history of sustained ventricular tachycardia were ex-cluded. Of this group, 37 patients (33 men, mean age 63⫾ 9) who underwent complete myocardial revas-cularization (14 with coronary artery bypass grafting and 23 with coronary angioplasty) within 1 month of the scintigraphic analysis were included in this study. The decision for revascularization was based on the independent judgment of the referring physician. All patients but 2 had a history of previous myocardial infarction.
Study protocol: All patients underwent in a single session resting and dobutamine nitrate-enhanced ses-tamibi-gated SPECT. Baseline resting sesses-tamibi-gated From the Division of Cardiology and Nuclear Medicine Unit,
Miseri-cordia e Dolce Hospital, Prato, Italy; and Nuclear Medicine Unit, Department of Clinical Physiopathology, University of Florence, Flo-rence, Italy. Manuscript received September 5, 2001; revised manu-script received and accepted December 14, 2001.
Address for reprints: Mario Leoncini, MD, Via del Cittadino 24,59100, Prato, Italy. E-mail: [email protected].
SPECT was repeated after revascularization (ⱖ3 months for bypass grafting and 1 month for coronary angioplasty) to assess global functional outcome and myocardial perfusion. Studies were performed after overnight fasting. Nitrates and-adrenergic blocking agents were withdrawn 48 hours before the tests. All patients gave informed consent to participate in the study, which was approved by the ethics committee of our institution.
Sestamibi-gated SPECT: The method of nitrate-en-hanced sestamibi imaging has been described.9,10One
hour after sestamibi (1,111 MBq, 30 mCi) injection, baseline resting gated SPECT was performed. Imme-diately thereafter, the dobutamine study was per-formed. Infusion was started at a dose of 5g/kg body weight/min and increased after 5 minutes to 10 g/ kg/min. Criteria for early interruption included hypo-tension, angina, or significant ventricular arrhythmia. Gated SPECT acquisition was started after 3 minutes of the 10-g dose, which was maintained until acqui-sition was completed. For the postrevascularization study, the same dose of sestamibi was injected at rest, followed 1 hour later by SPECT acquisition. A dual-head gamma camera (ADAC Vertex, Milpitas, Cali-fornia) equipped with high-resolution collimators and with a 15% window centered on the 140-keV photo-peak of technetium-99m was used for image collec-tion. SPECT was performed in step-and-shoot mode, with 32 projections over a 180° elliptical orbit, matrix size 64⫻ 64, 45 seconds/projection, 8 frames/cardiac cycle. The studies were reconstructed using filtered back-projection without attenuation or scatter correc-tion and realigned along the heart axis. For perfusion and functional analysis, the left ventricle was divided into 16 segments and 3 coronary territories were con-sidered.7,8Tracer uptake was quantified with an auto-matic program that calculated the mean uptake of each segment, identified the segment with peak uptake, set it to 100% activity, and scaled the other segments as a percentage of peak activity.10 Regional function was assessed visually by consensus of 2 experienced ob-servers and scored using a 4-point scale (1⫽ normal; 2⫽ hypokinesia; 3 ⫽ akinesia; 4 ⫽ dyskinesia).7,8,11
The reproducibility of regional functional scoring in our laboratory has been reported.7The assessment of
viability was restricted to the revascularized segments with abnormal function at rest (score 2 to 4). Two criteria for detecting viability were considered: ni-trate-sestamibi activity ⱖ50% in perfusion study,12
and contractile reserve on dobutamine-gated SPECT study (defined by a decrease ofⱖ1 grade in regional wall motion score during dobutamine administra-tion).7,8 Data processing and calculation of LV
end-diastolic and end-systolic volumes and LV ejection fraction were performed by an automated and vali-dated method.13 Significant improvement in global LV ejection fraction after revascularization was de-fined as an increase ofⱖ5 ejection fraction units in the follow-up control compared with the baseline val-ue.14,15
Statistical analysis: Results are expressed as mean
⫾ SD. The comparison of variables within and
be-tween groups was performed with the Student’s t test for paired or independent samples as appropriate. The comparison of proportions was made using the Fish-er’s exact test. The correlation between LV volumes and LV ejection fraction during dobutamine and after revascularization was calculated using Pearson’s cor-relation coefficient. The sensitivity and the specificity of dobutamine sestamibi-gated SPECT to predict an increase in LV ejection fraction after revascularization were calculated using receiver-operating characteris-tics curve analysis. A p value ⬍0.05 was considered statistically significant.
RESULTS
Gated SPECT after revascularization versus baseline gated SPECT:On follow-up gated SPECT, none of the patients had worsening of perfusion in the coronary territories submitted to revascularization. In the whole study cohort, mean LV ejection fraction improved from 34⫾ 10% before to 39 ⫾ 11% after revascular-ization (p⬍0.001). According to the changes in ejec-tion fracejec-tion, patients were divided into 2 groups: group A (19 patients) had improvement in LV ejection fraction ⱖ5 U after revascularization; group B (18 patients) did not have an increase in LV ejection fraction ⱖ5 U after revascularization. No significant differences in the 2 groups were observed regarding demographic, clinical, and instrumental variables (Ta-ble 1). Compared with baseline values, group A had a reduction in end-diastolic (p⬍0.05) and end-systolic (p ⬍0.002) volumes so that after revascularization these values were significantly lower than those ob-served in group B (Table 1). The mean number of viable asynergic segments was higher in group A than in group B (Table 2). With use of a threshold of⬎4 viable segments to identify patients with LV ejection fraction increaseⱖ5 U,15sestamibi activity achieved
89% sensitivity, 67% specificity, and 78% accuracy.
Dobutamine-gated SPECT:During dobutamine there was a marked variation (from –3 to ⫹19 ejection fraction units) of the LV ejection fraction with respect to baseline values. Mean dobutamine ejection fraction was 40⫾ 12% in group A (p ⬍0.001 vs baseline) and 35⫾ 13% in group B (p ⬍0.05 vs baseline). Accord-ing to receiver-operatAccord-ing characteristics curve analy-sis, the increase in LV ejection fractionⱖ5 U during dobutamine was the optimal cutoff value for predict-ing a significant postrevascularization increase. An improvement in ejection fractionⱖ5 U during dobut-amine was observed in 15 group A patients and in 4 group B patients (p⬍0.005). The dobutamine increase in LV ejection fraction ⱖ5 U predicted a significant increase in ejection fraction after revascularization, with a sensitivity, specificity, and overall accuracy of 79%, 78%, and 78%, respectively. The individual changes in LV ejection fraction at baseline, during dobutamine, and after revascularization are seen in Figure 1. A significant correlation was found between dobutamine LV ejection fraction and postrevascular-ization ejection fraction (r⫽ 0.85; p ⬍0.0001) (Figure 2). Moreover, there was a significant correlation
be-tween dobutamine end-diastolic (r ⫽ 0.86; p
⬍0.0001) and end-systolic (r ⫽ 0.89; p ⬍0.0001)
volumes and the related values after revascularization.
DISCUSSION
An important advantage of gated SPECT perfu-sion imaging over other methods is the possibility of obtaining data about myocardial perfusion and regional and global function during the same acqui-sition. The simultaneous assessment of perfusion and regional function improves the accuracy of simple perfusion study for the detection of myocar-dial viability.2– 4 Gated SPECT imaging may also
provide evaluation of wall motion and thickening changes during inotropic stimulation.5– 8 A good
agreement between gated SPECT and other imaging techniques in evaluating contractile reserve elicited by dobutamine infusion was demonstrated.5,7 In detecting hibernating viable myocardium, the as-sessment of contractile reserve adds diagnostic power to perfusion imaging, and the combination of perfusion and functional data significantly
im-proved the accuracy of sestamibi-gated SPECT for predicting re-gional reversible dysfunction.8
However, the most important clin-ical goal of coronary revasculariza-tion is improvement in global LV function.16 Global functional
im-provement after revascularization was correlated with the extent of viable myocardium, defined by the number of the asynergic segments with preserved cellular membrane integrity,17 maintained
metabo-lism,18 or contractile reserve.17,18 Also, according to our results, the group of patients with improved LV ejection fraction ofⱖ5 U after revascularization had significantly more revascularized viable asyner-gic segments with preserved cellu-lar membrane integrity or contrac-tile reserve than patients without significant LV ejection fraction im-provement. Gated SPECT also al-lows automated calculation of LV volumes and ejection fraction, which can be esti-mated in a reliable and reproducible way.1 The
results of this study suggest that dobutamine ejec-tion fracejec-tion changes predict global funcejec-tional re-sponse after revascularization. A global increase of at least 5 U in LV ejection fraction in response to dobutamine is a good predictor of a significant increase in LV ejection fraction after intervention. The relation between dobutamine-induced and pos-trevascularization ejection fraction changes con-firms and expands the results of previous studies performed using more established imaging tech-niques.18 –20 Zafrir et al20 found that dobutamine ra-dionuclide ventriculography had a sensitivity of 67% and specificity of 93% for predicting improvement in global LV function after revascularization. In the study of Sanchis et al,19dobutamine contrast ventricu-lography predicted an increase in LV ejection fraction after revascularization with sensitivity and specificity of 80% and 83%, respectively. Using dobutamine echocardiography, Pasquet et al18obtained a sensitiv-ity of 93% and specificsensitiv-ity of 90% for the prediction of ejection fraction outcome. The increase in LV ejection fraction during dobutamine echocardiography was a stronger predictor of overall improvement in post-revascularization ejection fraction than either the number of viable asynergic segments identified by maintained metabolism or preserved contractile re-serve.18In our study, dobutamine LV ejection fraction showed a good diagnostic accuracy (79% sensitivity and 78% specificity) for significant global function improvement after revascularization. These results confirm that dobutamine-induced ejection fraction changes provide important diagnostic information for assessing myocardial viability in patients with isch-emic cardiomyopathy. This information can be easily achieved using gated SPECT together with
quantifi-TABLE 1 Comparison of Clinical, Angiographic, and Scintigraphic Characteristics
Between Patients With (group A) and Without (group B) Improvement ofⱖ5 U in LV Ejection Fraction After Revascularization
Variable
Group A (n⫽ 19)
Group B
(n⫽ 18) p Value Mean age (yrs) 64⫾ 9 63⫾ 10
Previous myocardial infarction
Anterior 12 14
Inferior 5 4
No. of narrowed coronary arteries
1 7 9 2–3 12 9 Mode of revascularization Coronary angioplasty 10 13 Coronary bypass 9 5 Ejection fraction (%) Baseline 34⫾ 9 33⫾ 12 Postrevascularization 44⫾ 8* 32⫾ 11 ⬍0.001 End-diastolic volume (ml) Baseline 168⫾ 69 201⫾ 66 Postrevascularization 149⫾ 52† 195⫾ 62 0.01 End-systolic volume (ml) Baseline 116⫾ 68 141⫾ 68 Postrevascularization 86⫾ 45‡ 135⫾ 99 0.01
*p⬍0.00001 versus baseline;†p⫽ 0.03 versus baseline;‡p⫽ 0.001 versus baseline.
TABLE 2 Comparison of Revascularized Asynergic Segments
Classified as Viable According to Sestamibi Activity and Contractile Reserve in Patients With (group A) Versus Without (group B) Improvement ofⱖ5 U in LV Ejection Fraction After Revascularization
Group A Group B Sestamibi activityⱖ50%
All asynergic segments 7⫾ 2.9 4⫾ 3* Adyskinetic segments 3⫾ 1.7 2⫾ 1.6† Contractile reserve
All asynergic segments 3.9⫾ 2.6 2⫾ 1.7†
cation of regional perfusion and evaluation of regional contractile reserve.
The results of the present study must be evaluated cautiously because of several limitations. A general limitation of gated SPECT is that it cannot be used in patients with atrial fibrillation or frequent ectopic beats. As in many other studies using postrevascular-ization global functional recovery as the reference standard to define myocardial viability, the patient group is quite small. Angiography was not performed at follow up; thus, silent restenosis or graft occlusion could not be completely ruled out, although resting per-fusion was maintained or improved. However, recurrent ischemia was excluded by clinical observation and neg-ative exercise stress testing whenever necessary.
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dobut-amine.
FIGURE 2. Correlation between LV ejection fraction during dobutamine stimulation and after revascularization. Abbreviation as in Figure 1.
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